Management of Advanced Systemic Mastocytosis: Clinical Challenges

Douglas Tremblay,1 Nicole E Wagner,2 John Mascarenhas1 1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USACorrespondence: John Mascarenhas, Myeloproliferative Disorders Program, Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1079, New York, NY, 10029, USA, Tel +1 212 241 3417, Fax +12128765276, Email [email protected]: Advanced systemic mastocytosis (AdvSM) is a rare hematologic malignancy with organ damage and compromised life expectancy arising from organ accumulation of neoplastic mast cells. Identification of the gain-of-function KITD816V in the majority of cases has accelerated pharmaceutical development culminating with the development of selective KIT inhibitors such as avapritinib. While the advent of these therapies has improved the quality and quantity of life in patients with AdvSM, current challenges remain in the management of this disease. In this review, we summarize the present and future therapeutics landscape of AdvSM, highlighting the development of novel KIT inhibitors including elenestinib and bezuclastinib. We also explore the continued role of additional treatment modalities including allogeneic stem cell transplantation before discussing unresolved clinical challenges in the management of AdvSM.Keywords: systemic mastocytosis, KITD816V, avapritinib, midostaurin